The objectives of the proposed research are to: 1) Study the genetics of the effect of the H-2 locus on relative resistance to local tumorigenesis by the chemical carcinogen 3-methylcholanthrene (MCA). 2) Determine if the mechanism of this effect involves interallelic interactions or (as has been shown for viral leukemogenesis) cell surface interactions between tumor antigens and H-2-alloantigens. To these ends we are: 1) Studying the induction of local tumors by MCA in normal and T cell deficient mice differing genetically only at the H-2 locus or portions thereof (i.e., recombinant H-2 haplotypes) and their F1 progeny. 2) Establishing lines of H-2 loss variant cells from cloned tumor cells induced by MCA in mice heterozygous only with respect to the H-2 locus. These H-2 loss variants and their parental H-2 heterozygous cells will be used to determine if MCA-induced tumor associated antigens and H-2 alloantigens interact physically on the cell membrane. The results of these studies will either support or negate the hypothesis that relative resistance to local tumorigenesis by MCA involves T cell recognition of "altered-H-2" or "hybrid antigen" resulting from cell surface interaction between tumor and H-2 alloantigen molecules.